Iridoids transformation

Electro-decarboxylation of endo-3-methoxycarbonyl-7-oxabicyclo[2.2. l]heptane-endo-2-carboxylic acid 20 in an MeOH—MeONa—(C) system gives exclusively an oxygen-assisted Wagner-Meerwein rearrangement via the intermediate carbenium ion forming 21 in 83% yield 54). Product 21 can be transformed to iridoid monoterp-enes 22 (Scheme 3-7)54a). 

Tissue Cultures, Microbial Transformations.—Little success has rewarded the search for cell cultures that effectively biosynthesize monoterpenes de novo. The most impressive studies utilize cultures from a variety of Mentha spp. yields of oil were some 60 % (w/v) of those in the parent plants, but the monoterpene products were generally more oxidized (i.e. ketones extra C=C bonds predominated). In vitro, oxidation at C-3 of the menthane skeleton was also restricted, apparently owing to an inhibition of the enzymic reduction of the 4(8) double bond in the intermediates formed.925 926 Colchicine stimulated synthesis of essential oil by Mentha cultures.927 Iridoid glucosides have been produced by cultured cells of Gardenia spp.673 Menthone was biotransformed to neomenthol by Mentha suspension cultures,928 and Nicotiana lines oxidized linalool and its derivatives at C-10 to aldehydes and alcohols,929 and also foreign substrates such as a-terpineol (at C-6 and C-7) and /raw.s-/ -menthan-9-en-l-ol (at C-4 and C-10).930... 

Following the isolation and structure elucidation of rhexifoline (23) from Castilleja rhexifolia (35), further work on the flower heads yielded three iridoid glucosides, one of which was penstemonoside (302). Recognizing the potential relationship between 23 and 302, Roby and Stermitz carried out the synthetic transformation of 302 to 23 (81). Treatment of penstemonoside (302) with /3-glucosidase afforded a 2 1 epimeric mixture of the lactol 303. Reaction with methanolic HC1 followed by ammonia afforded rhexifoline (23) in 31% overall yield (Scheme 30) (81). Euphroside (304), the principal iridoid of Orthocarpus spp., was used for the structure confirmation of euphrosine (25) (40). Acid hydrolysis of 304 in methanol afforded 305, which was treated with aqueous acid followed by basification with ammonia to afford a low yield of euphrosine (25), identical with the natural product (Scheme 31) (40). 

I. Human Fecal Flora and Intestinal Bacteria for the Transformation of Iridoid Glucosides... 

Up to now, all the species of the tribe Oleaceae contain oleoside-type iridoids, which are also present in the group of species Jasminum. of Jasmineae. In both tribes, these oleosides may be hydroxylated at C-10, even though, in genus as Syringa and many species of the Jasminum group, this transformation is not present. 

The hemiacetalic iridoidic intermediate 49 obtained has been successively transformed into the two corresponding enantiomers methylacetals 50 and 50a and the secondary alcoholic function on the cyclopentane ring oxidised to a carbonyl group (enantiomeric mixture 51 and 51a obtained). 

Koizumi and coworkers have developed a new enantiomerically pure a,p-unsaturated sulfoxide dienophile bearing the isoborneol group as a chiral auxiliary, dimethyl (f )-2-(10-isoborneolsulfinyl)maleate (214), which has been successfully employed as a chiral synthetic equivalent of dimethyl acetylenedicarboxylate [174], The dienophile (214) underwent cycloaddition with cyclopentadiene, in the presence of zinc chloride, with high stereo- and diastereoselectivity (92% single endo diastereoisomer, 6% single exo diastereoisomer) to yield the major cycloadduct (215), which was subsequently transformed into the half-ester (216), an intermediate in the syntheses of (-)-aristeromycin (199) and (-)-neplanocin A (200). Cycloadduct (215) has also recently been used for the synthesis of bicyclo[2.2.1]heptane lactone (217) [175,177], which itself is an intermediate in the synthesis of the iridoid (-)-boschnialactone [176] (218) (Scheme 5.69), and also in the formal synthesis of (-)-aristeromycin (199) and (-)-neplanocin (200) [177]. 

A key intermediate in the biosynthesis of all iridoid indole alkaloids is the glu-coside strictosidine (isovincoside. Fig. 260). Strictosidine is transformed to aj-malicine, which is a precursor of stemmadenine, tabersonine, vindoline and catharanthine (Fig. 261). The dimeric alkaloids, like vinblastine (vincaleuco-blastine) and vincristine (Fig. 259) are derived from monomeric precursors, e.g. catharanthine and vindoline. 

Iridoids are a large and stmcturally diverse class of secondary metabolites of monoterpenoid origin [10, 11]. Their sttuc-tural parent system is the iridane skeleton, which is derived from geraniol (6) by a cyclization pathway that is mechanistically different to the cyclization reactions that are usually found in classical terpene chemistry [1, 12], Further enzymatic transformations then give the fundamental iridoid skeleton or the thereof derived secoiridoid motive (with an alternative connectivity as shown in Scheme 6.10), which often serves as a building block for the synthesis of more complex monoterpenoid indole alkaloids [1]. Noteworthy, hereby the isoprene mle is often not fulfilled anymore as the terpenoid parts of such compounds sometimes contain nine carbon atoms only due to a decarboxylation step somewhere in the sequence. Very often iridoids and secoiridoids are present as glycosides in nature. 

SCHEME 642 Proline-catalyzed transformations in the total syntheses of (-)-brasoside (262) and (-)-littoralisone (263) proceeding via the iridoid 264. 

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